Treatment of breast cancer with different antiprogestins: preclinical and clinical studies.
Treatment with antiprogestins is a new treatment modality for breast cancer. Previously, in rats with DMBA-induced mammary tumors we observed significant growth inhibitory effects of chronic treatment with the antiprogestin mifepristone (RU486). In addition, in 11 postmenopausal breast cancer patients, we observed one objective response, six instances of short-term stable disease, and four instances of progressive disease. Side-effects appeared mainly due to antiglucocorticoid properties of the drug. Increased plasma estradiol levels were observed which probably resulted from ovarian (rat) and adrenal (patients) steroidogenesis. Combined treatment with an antiestrogen in the rat model caused additive growth inhibitory effects. Tumor inhibition after single treatment with mifepristone or tamoxifen was 90 and 75%, respectively. In contrast, when combined, tumor remission similar to that caused by LHRH-agonist treatment (50%) was observed. Even higher tumor remission was found after combined treatment with mifepristone plus LHRH-agonist (75%). In first studies in the rat model we observed significant tumor growth inhibitory effects with two new antiprogestins of seemingly greater potency which cause less unfavorable endocrine side-effects.


CONCLUSIONS
combined treatment (antiprogestin plus antiestrogen or LHRH-agonist) may be of value in endocrine therapy of breast cancer.
Bakker
G H
GH
Division of Endocrine Oncology, Biochemistry and Endocrinology, Dr Daniel Den Hoed Cancer Center, Rotterdam, The Netherlands.
Setyono-Han
B
B
Portengen
H
H
De Jong
F H
FH
Foekens
J A
JA
Klijn
J G
JG
D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006728:Hormones / Q000097:blood; D006801:Humans; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology*; D009929:Organ Size; D051381:Rats; D011987:Receptors, Steroid / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D006728:Hormones; D011987:Receptors, Steroid; D013629:Tamoxifen; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone